Evaluation of the Neonatal Sequential Organ Failure Assessment and Mortality Risk in Preterm Infants With Late-Onset Infection.

Importance: Infection in neonates remains a substantial problem. Advances for this population are hindered by the absence of a consensus definition for sepsis. In adults, the Sequential Organ Failure Assessment (SOFA) operationalizes mortality risk with infection and defines sepsis. The generalizability of the neonatal SOFA (nSOFA) for neonatal late-onset infection-related mortality remains unknown. Objective: To determine the generalizability of the nSOFA for neonatal late-onset infection-related mortality across multiple sites. Design, Setting, and Participants: A multicenter retrospective cohort study was conducted at 7 academic neonatal intensive care units between January 1, 2010, and December 31, 2019. Participants included 653 preterm (<33 weeks) very low-birth-weight infants. Exposures: Late-onset (>72 hours of life) infection including bacteremia, fungemia, or surgical peritonitis. Main Outcomes and Measures: The primary outcome was late-onset infection episode mortality. The nSOFA scores from survivors and nonsurvivors with confirmed late-onset infection were compared at 9 time points (T) preceding and following event onset. Results: In the 653 infants who met inclusion criteria, median gestational age was 25.5 weeks (interquartile range, 24-27 weeks) and median birth weight was 780 g (interquartile range, 638-960 g). A total of 366 infants (56%) were male. Late-onset infection episode mortality occurred in 97 infants (15%). Area under the receiver operating characteristic curves for mortality in the total cohort ranged across study centers from 0.71 to 0.95 (T0 hours), 0.77 to 0.96 (T6 hours), and 0.78 to 0.96 (T12 hours), with utility noted at all centers and in aggregate. Using the maximum nSOFA score at T0 or T6, the area under the receiver operating characteristic curve for mortality was 0.88 (95% CI, 0.84-0.91). Analyses stratified by sex or Gram-stain identification of pathogen class or restricted to infants born at less than 25 weeks' completed gestation did not reduce the association of the nSOFA score with infection-related mortality. Conclusions and Relevance: The nSOFA score was associated with late-onset infection mortality in preterm infants at the time of evaluation both in aggregate and in each center. These findings suggest that the nSOFA may serve as the foundation for a consensus definition of sepsis in this population.

Reconsidering Strategies for Managing Chronic Periprosthetic Joint Infection in Total Knee Arthroplasty: Using Decision Analytics to Find the Optimal Strategy Between One-Stage and Two-Stage Total Knee Revision.

BACKGROUND: Periprosthetic joint infection (PJI) following total knee arthroplasty is a growing concern, as the demand for total knee arthroplasty (TKA) expands annually. Although 2-stage revision is considered the gold standard in management, there is substantial morbidity and mortality associated with this strategy. One-stage revision is associated with lower mortality rates and better quality of life, and there has been increased interest in utilizing the 1-stage strategy. However, surgeons are faced with a difficult decision regarding which strategy to use to treat these infections, considering uncertainty with respect to eradication of infection, quality of life, and societal costs with each strategy. The purpose of the current study was to use decision analysis to determine the optimal decision for the management of PJI following TKA. METHODS: An expected-value decision tree was constructed to estimate the quality-adjusted life-years (QALYs) and costs associated with 1-stage and 2-stage revision. Two decision trees were created: Decision Tree 1 was constructed for all pathogens, and Decision Tree 2 was constructed solely for difficult-to-treat infections, including methicillin-resistant infections. Values for parameters in the decision model, such as mortality rate, reinfection rate, and need for additional surgeries, were derived from the literature. Medical costs were derived from Medicare data. Sensitivity analysis determined which parameters in the decision model had the most influence on the optimal strategy. RESULTS: In both decision trees, the 1-stage strategy produced greater health utility while also being more cost-effective. In the Monte Carlo simulation for Decision Trees 1 and 2, 1-stage was the dominant strategy in about 85% and 69% of the trials, respectively. Sensitivity analysis showed that the reinfection and 1-year mortality rates were the most sensitive parameters influencing the optimal decision. CONCLUSIONS: Despite 2-stage revision being considered the current gold standard for infection eradication in patients with PJI following TKA, the optimal decision that produced the highest quality of life was 1-stage revision. These results should be considered in shared decision-making with patients who experience PJI following TKA. LEVEL OF EVIDENCE: Economic and Decision Analysis Level IV. See Instructions for Authors for a complete description of levels of evidence.

Impact of an infectious diseases specialist-led antimicrobial stewardship programmes on antibiotic use and antimicrobial resistance in a large Korean hospital.

The aim of this study was to evaluate the impact of an infectious diseases specialist (IDS)-led antimicrobial stewardship programmes (ASPs) in a large Korean hospital. An interrupted time series analysis assessing the trends in antibiotic use and antimicrobial resistance rate of major pathogens between September 2015 and August 2017 was performed in an 859-bed university-affiliated hospital in Korea. The restrictive measure for designated antibiotics led by an IDS reduced carbapenems usage by -4.57 days of therapy (DOT)/1,000 patient-days per month in general wards (GWs) (95% confidence interval [CI], -6.69 to -2.46; P < 0.001), and by -41.50 DOT/1,000 patient-days per month in intensive care units (ICUs) (95% CI, -57.91 to -25.10; P < 0.001). Similarly, glycopeptides usage decreased by -2.61 DOT/1,000 patient-days per month in GWs (95% CI, -4.43 to -0.79; P = 0.007), and -27.41 DOT/1,000 patient-days per month in ICUs (95% CI, -47.03 to -7.79; P = 0.009). Use of 3rd generation cephalosporins, beta-lactam/beta-lactamase inhibitors, and fluoroquinolones in GWs showed change comparable with that of carbapenems or glycopeptides use. Furthermore, trends of antimicrobial resistance rate of Staphylococcus aureus to gentamicin in GWs, Staphylococcus aureus to ciprofloxacin and oxacillin in ICUs, and Pseudomonas aeruginosa to imipenem in ICUs decreased in slope in the intervention period. The in-hospital mortality rate per 1,000 patient-days among ICU patients remained stable between the pre-intervention and intervention periods. In conclusion, an IDS-led ASPs could enact a meaningful reduction in antibiotic use, and a decrease in antibiotic resistance rate, without changing mortality rates in a large Korean hospital.

10-year trends in vancomycin-resistant enterococci among allogeneic hematopoietic cell transplant recipients.

OBJECTIVES: We examined VRE colonization, bacteremia (VREB) incidence and outcomes within 100 days of allogeneic hematopoietic cell transplantation (HCT). METHODS: HCT recipients screened for VRE were assessed, and colonization and VREB incidence compared over time using linear regression. Cox proportional hazards models were constructed to assess the relationship between mortality, pre-HCT colonization, and underlying disease. RESULTS: Of 1492 HCT recipients, 204 (14%) patients were colonized pre-HCT, while 90 (6%) acquired colonization post-HCT. Forty-two patients (2.8%) developed VREB within 100 days post-HCT; the majority, 32 (76%), were previously colonized. The cumulative incidence of VREB was 2.9 per 10,000 patient-days. Over the study period there were no significant changes in incidence of VRE colonization or VREB despite a number of interventions (p > 0.1). Patients with pre-HCT colonization had increased mortality compared to non-colonized patients (HR 2.1; 95% CI: 1.5, 3.3). CONCLUSIONS: We found a low burden of VRE at our center with no significant changes observed over a 10-year study period. VRE, while responsible for substantial resource consumption from routine screening and isolation, was an infrequent cause of bacteremia.

The Risk Factors, Costs, and Survival Analysis of Invasive VRE Infections at a Medical Center in Eastern Taiwan.

OBJECTIVE: To analyze 48 cases the risk factors of vancomycin-resistant Enterococcus (VRE) infections, the antibiotic costs after infection, and the survival conditions. DESIGN: 1:3 matched case-control study a medical center in the eastern Taiwan area. The case group, patients with VRE bacterial strains detected at the sterile sites, and the control group were randomly selected from invasive vancomycin-sensitive Enterococcus (VSE) infected patients at the nearest time point by taking the occurrence time of each VRE infection case as the reference time. Fisher exact tests were conducted in order to verify the existence of differences between the case and control groups; survival analysis was applied to explore the prognoses of the VRE infection cases. RESULTS: The mortality rate of the invasive VRE infection cases was 64.6%, which is obviously higher than that of the invasive VSE infection cases (39.4%); the fact of taking chemotherapy during a hospital stay as well as the use of third-generation cephalosporin, glycopeptides, and medicines of the metronidazole category before the infections, are the risk factors of future invasive VRE infections. Moreover, the antibiotic costs after the infections of invasive VRE infection cases are much higher than those of the VSE infection cases (the average daily cost is 3,433 new Taiwan dollars (NTD) vs. 1,742 NTD). CONCLUSIONS: The history of receiving chemotherapy, the use of third-generation cephalosporin, glycopeptides, and medicines of the metronidazole category before the infections are the risk factors of VRE infections. The antibiotic costs after the infections of invasive VRE infection cases are much higher than those of the VSE infection cases.

Epidemiology, Management, and Risk-Adjusted Mortality of ICU-Acquired Enterococcal Bacteremia.

BACKGROUND: Enterococcal bacteremia has been associated with high case fatality, but it remains unknown to what extent death is caused by these infections. We therefore quantified attributable mortality of intensive care unit (ICU)-acquired bacteremia caused by enterococci. METHODS: From 2011 to 2013 we studied consecutive patients who stayed >48 hours in 2 tertiary ICUs in the Netherlands, using competing risk survival regression and marginal structural modeling to estimate ICU mortality caused by enterococcal bacteremia. RESULTS: Among 3080 admissions, 266 events of ICU-acquired bacteremia occurred in 218 (7.1%) patients, of which 76 were caused by enterococci (incidence rate, 3.0 per 1000 patient-days at risk; 95% confidence interval [CI], 2.3-3.7). A catheter-related bloodstream infection (CRBSI) was suspected in 44 (58%) of these, prompting removal of 68% of indwelling catheters and initiation of antibiotic treatment for a median duration of 3 (interquartile range 1-7) days. Enterococcal bacteremia was independently associated with an increased case fatality rate (adjusted subdistribution hazard ratio [SHR], 2.68; 95% CI, 1.44-4.98). However, for patients with CRBSI, case fatality was similar for infections caused by enterococci and coagulase-negative staphylococci (CoNS; adjusted SHR, 0.91; 95% CI, .50-1.67). Population-attributable fraction of mortality was 4.9% (95% CI, 2.9%-6.9%) by day 90, reflecting a population-attributable risk of 0.8% (95% CI, .4%-1.1%). CONCLUSIONS: ICU-acquired enterococcal bacteremia is associated with increased case fatality; however, the mortality attributable to these infections is low from a population perspective. The virulence of enterococci and CoNS in a setting of CRBSI seems comparable.

Vancomycin-resistant Enterococcus colonization in the intensive care unit: clinical outcomes and attributable costs of hospitalization.

BACKGROUND: The clinical and economic impact of vancomycin-resistant Enterococcus (VRE) colonization remains unclear. Little data are available on factors affecting hospitalization length of stay (LOS) and costs. This study aimed to estimate mortality, LOS, and hospitalization costs for VRE colonized patients compared with a matched hospital population. METHODS: We performed a retrospective propensity score matched cohort study comparing the outcomes of patients with VRE colonization with those of uncolonized subjects matched at the time they were admitted to the intensive care unit (ICU). Between January 2008 and December 2010, we obtained rectal swab cultures within 24 hours of ICU admission to detect VRE colonization. RESULTS: During the study period, 567 (7.2%) of the 7,703 patients were colonized with VRE. There were 199 VRE colonized patients compared with 199 uncolonized patients using the propensity score. VRE colonized patients when compared with uncolonized patients were likely to have a higher case fatality rate (24.6% vs 17.1%; OR, 2.35). Longer total admission days were observed in the VRE colonized patients (28.7 vs 21.4 days; multiplicative effect, 1.25; P = .004). VRE colonization is found to be a significant factor associated with increased ICU cost in the multivariable regression model ($6,065 vs $5,298; multiplicative effect, 1.22; P = .029). Multivariable analysis identified the factors affecting ICU cost as follows: VRE colonization (odds ratio [OR], 1.20; P = .038), ICU length of stay (OR, 1.93; P < .001), ICU type (OR, 1.51; P = .001), valvular heart disease (OR, 2.38; P = .27), hospitalization within 12 months (OR, 1.21; P = .037), and use of invasive devices (OR, 1.28; P = .017). CONCLUSION: Compared with a matched hospital population, VRE colonization was associated with increased mortality, LOS, and costs. Strict infection control programs, including preemptive isolation for a high-risk group, should be helpful.

[Bacteraemia at a second level hospital: epidemiological study, analysis of pronostic factors associated to mortality and economic cost estimation]. / Bacteriemias en un hospital de segundo nivel: estudio epidemiológico, análisis de factores pronósticos asociados a mortalidad y estimación de su coste económico.

INTRODUCTION: Bacteraemia (B) accounts for a considerable proportion (0.36%) of all hospital admissions due to infections diseases and it is associated to increased hospital costs. The aim of this study is to describe a cohort of patients with bacteraemia at a second level hospital, to analyze factors associated to mortality and its economical impact during hospital admission. PATIENTS AND METHODS: Observational study of a cohort of adult patients with bacteraemia admitted at a second level hospital during 2010. Data collection from clinical records has been done according to a standard protocol: epidemiological and clinical variables and factors associated to mortality were analysed. Total economical cost per patient was estimated. RESULTS: 148 patients were included: 80 community B (55.4%), 23 health care associated B (15.5%) and 45 nosocomial B (28.5%). The incidence was 9 cases 10.000 persons/year. Mean age was 69 years and the global mortality was 24%. In bivariate analysis smoking, diabetes mellitus, McCabe Jackson score type I-II, Pitt Index ≥ 3, APACHE ≥ 20, Glasgow ≤ 9, shock, respiratory distress, invasive procedures, nosocomial bacteraemia and inadequate empiric or definitive antibiotic treatment were associated to mortality (p<0.05). Factors associated to mortality in multivariate analysis included McCabe Jackson score type I-II (OR 4.95; 95% CI 1.095-22.38), haemodialysis during acute stage (OR 7.8; 95% CI 2.214-27.773) and inadequate empiric antibiotic treatment (OR 7.68; 95% CI 19.82-29.77). Admission economic cost per patient was 9,459 € for community acquired bacteriemia, 5,656 € for health care associated bacteraemia and 41,680€ for nosocomial bacteraemia. CONCLUSIONS: Comorbidity, inadequate empiric antibiotic treatment and haemodialysis during acute phase are statistically significantly in our cohort of patients with bacteraemia.

Enterococcal bacteraemia: factors influencing mortality, length of stay and costs of hospitalization.

Enterococci are a major cause of nosocomial bacteraemia. The impacts of vanB vancomycin resistance and antibiotic therapy on outcomes in enterococcal bacteraemia are unclear. Factors that affect length of stay (LOS) and costs of managing patients with enterococcal bacteraemia are also unknown. This study aimed to identify factors associated with mortality, LOS and hospitalization costs in patients with enterococcal bacteraemia and the impact of vancomycin resistance and antibiotic therapy on these outcomes. Data from 116 patients with vancomycin-resistant Enterococci (VRE), matched 1:1 with patients with vancomycin-susceptible Enterococcus (VSE), from two Australian hospitals were reviewed for clinical and economic outcomes. Univariable and multivariable logistic and quantile regression analyses identified factors associated with mortality, LOS and costs. Intensive care unit admission (OR, 8.57; 95% CI, 3.99-18.38), a higher burden of co-morbidities (OR, 4.55; 95% CI, 1.83-11.33) and longer time to appropriate antibiotics (OR, 1.02; 95% CI, 1.01-1.03) were significantly associated with mortality in enterococcal bacteraemia. VanB vancomycin resistance increased LOS (4.89 days; 95% CI, 0.56-11.52) and hospitalization costs (AU$ 28 872; 95% CI, 734-70 667), after adjustment for confounders. Notably, linezolid definitive therapy was associated with lower mortality (OR, 0.13; 95% CI, 0.03-0.58) in vanB VRE bacteraemia patients. In patients with VSE bacteraemia, time to appropriate antibiotics independently influenced mortality, LOS and hospitalization costs, and underlying co-morbidities were associated with mortality. The study findings highlight the importance of preventing VRE bacteraemia and the significance of time to appropriate antibiotics in the management of enterococcal bacteraemia.

Institutional perspective on the impact of positive blood cultures on the economic and clinical outcomes of patients with complicated skin and skin structure infections: focus on gram-positive infections.

BACKGROUND: Traditionally, skin and skin structure infections (SSSIs) have been viewed as having a lower risk of mortality, morbidity, and cost compared with other types of infection. The influence of secondary bacteremia on the medicoeconomic outcomes of patients with SSSIs has not been well described. OBJECTIVE: The goal of this study was to evaluate the impact of bacteremia complicating SSSIs on length of hospital stay and costs. METHODS: This was a retrospective cohort study involving 579 patients with culture-positive SSSIs who were admitted to Barnes-Jewish Hospital, a major academic medical center, between April 1, 2005, and December 31, 2007. The outcomes evaluated in this analysis included hospital mortality, length of stay, hospital costs, and hospital readmission. RESULTS: Secondary bacteremia was present in 277 (47.8%) patients. Hospital mortality was statistically greater among patients with bacteremia (7.9% vs 1.0%; P < 0.001). The unadjusted median length of stay in bacteremic patients was 7.1 days compared with 2.8 days in those without bacteremia (P < 0.001 by log-rank test). This finding correlated with total hospital costs, which were greater in patients with bacteremia (median values: $14,623 vs $5841.50; P < 0.001). In a Cox model controlling for multiple confounders, bacteremia independently correlated with hospital duration (adjusted hazard ratio [HR], 1.820; 95% CI, 1.654-2.003; P < 0.001) and hospital costs (adjusted HR, 1.895; 95% CI, 1.723-2.083; P < 0.001). Hospital readmission within 30 days of discharge was also significantly more common among patients with SSSIs complicated by bacteremia (24.5% vs 12.9%; P < 0.001). CONCLUSIONS: Bacteremia complicating SSSIs occurred in almost 50% of patients infected with gram-positive bacteria in our institution. Beyond its impact on mortality, bacteremia is associated with increased length of stay, hospital costs, and readmission. However, these data are from a single academic medical center and may not be adjusted for all applicable confounders.

Human health risk assessment of penicillin/aminopenicillin resistance in enterococci due to penicillin use in food animals.

Penicillin and ampicillin drugs are approved for use in food animals in the United States to treat, control, and prevent diseases, and penicillin is approved for use to improve growth rates in pigs and poultry. This article considers the possibility that such uses might increase the incidence of ampicillin-resistant Enterococcus faecium (AREF) of animal origin in human infections, leading to increased hospitalization and mortality due to reduced response to ampicillin or penicillin. We assess the risks from continued use of penicillin-based drugs in food animals in the United States, using several assumptions to overcome current scientific uncertainties and data gaps. Multiplying the total at-risk population of intensive care unit (ICU) patients by a series of estimated factors suggests that not more than 0.04 excess mortalities per year (under conservative assumptions) to 0.14 excess mortalities per year (under very conservative assumptions) might be prevented in the whole U.S. population if current use of penicillin drugs in food animals were discontinued and if this successfully reduced the prevalence of AREF infections among ICU patients. These calculations suggest that current penicillin usage in food animals in the United States presents very low (possibly zero) human health risks.

Clinical impact of antibiotic-resistant Gram-positive pathogens.

The European Union's attention to the problem of antibacterial resistance will soon reach a 10-year mark, but the rates of resistance in Gram-positive and Gram-negative bacteria are still increasing. This review focuses on the clinical impact of resistant Gram-positive bacteria on patients. Multiple drug resistance in pneumococcal infections will lead to more treatment failures and higher mortality, which so far have been seen with penicillins and pathogens with high-level resistance. Several studies have demonstrated higher mortality, prolonged length of hospital stay and higher costs associated with methicillin-resistant Staphylococcus aureus infections, in comparison with methicillin-susceptible Staphylococcus aureus infections. Similarly, vancomycin-resistant enterococci bloodstream infections have a negative impact with respect to mortality, length of hospital stay and costs, in comparison with infections due to vancomycin-susceptible enterococci. Several distinctive prophylactic and therapeutic approaches have to be undertaken to successfully prevent the clinical consequences of antibiotic resistance in Gram-positive bacteria. This review addresses the impact of antibiotic-resistant Gram-positive pathogens on clinical outcomes.

Review of studies of the impact on Gram-negative bacterial resistance on outcomes in the intensive care unit.

OBJECTIVE: To review studies addressing mortality, length of stay (LOS), and cost of resistant Gram-negative bacterial infections in the intensive care unit (ICU). DATA SOURCES AND STUDY SELECTION: A qualitative review of published studies identified through PubMed search was performed. Study exclusion criteria were population <40 adults or <39% of cases in the ICU. Criteria for judging study quality were prospective analysis, multicenter study, author-specified diagnostic criteria, appropriate control group defined as patients with infections caused by susceptible bacteria, adjustments for confounding factors, and use of cost. DATA EXTRACTION AND SYNTHESIS: Twenty-one original studies and a meta-analysis, which included three of the original studies, were identified. Infections caused by mixed resistant Gram-negative bacteria, extended-spectrum beta-lactamase-producing Enterobacteriaceae, multidrug-resistant Pseudomonas aeruginosa, and Acinetobacter species were generally associated with increased mortality and LOS, especially in univariate analyses. Economic analyses performed in eight studies indicated that these resistant Gram-negative infections were also associated with increased patient charges or hospital costs. Associations sometimes disappeared in multivariate analyses after adjusting for variables significant in univariate analyses. CONCLUSION: The collective findings of the studies in this review suggested that Gram-negative bacterial resistance increases the burden in the ICU as measured by mortality, LOS, and charges. More prospective studies are needed to explore methods for combating Gram-negative resistance, including prevention, education, and better antimicrobial therapy. For example, well-designed research is needed to determine the cost-effectiveness of appropriate empiric therapy with broad-spectrum agents active against resistant Gram-negative bacteria followed by de-escalation.

Clinical and economic burden of antimicrobial resistance.

Knowledge of the clinical and economic impact of antimicrobial resistance is useful to influence programs and behavior in healthcare facilities, to guide policy makers and funding agencies, to define the prognosis of individual patients and to stimulate interest in developing new antimicrobial agents and therapies. There are a variety of important issues that must be considered when designing or interpreting studies into the clinical and economic outcomes associated with antimicrobial resistance. One of the most misunderstood issues is how to measure cost appropriately. Although imperfect, existing data show that there is an association between antimicrobial resistance in Staphylococcus aureus, enterococci and Gram-negative bacilli and increases in mortality, morbidity, length of hospitalization and cost of healthcare. Patients with infections due to antimicrobial-resistant organisms have higher costs (US $6,000-30,000) than do patients with infections due to antimicrobial-susceptible organisms; the difference in cost is even greater when patients infected with antimicrobial-resistant organisms are compared with patients without infection. Given limited budgets, knowledge of the clinical and economic impact of antibiotic-resistant bacterial infections, coupled with the benefits of specific interventions targeted to reduce these infections, will allow for optimal control and improved patient safety. In this review, the authors discuss a variety of important issues that must be considered when designing or interpreting studies of the clinical and economic outcomes associated with antimicrobial resistance. Representative literature is reviewed regarding the associations between antimicrobial resistance in specific pathogens and adverse outcomes, including increased mortality, length of hospital stay and cost.

Mortality associated with bloodstream infection after coronary artery bypass surgery.

BACKGROUND: Mortality attributable to bloodstream infection (BSI) is still controversial. We studied the impact of BSI on mortality after coronary artery bypass surgery, including the specific impact of different etiologic organisms. METHODS: Our cohort consisted of 4515 patients who underwent coronary artery bypass procedures at a university hospital from 1996 through 2004. We used Society of Thoracic Surgery data supplemented with laboratory and infection control data. Mortality dates were identified using Society of Thoracic Surgery data and the Social Security Death Index. BSI within 90 days after surgery was defined by a positive blood culture result. Cox proportional hazards and propensity score models were used to analyze the association between BSI and mortality. RESULTS: Patients with BSI had a 4.2-fold increased risk of death (95% confidence interval [CI], 3.0-5.9) 2-90 days after coronary artery bypass surgery, compared with uninfected patients. The risk of death was higher among patients with BSI due to gram-negative bacteria (hazard ratio [HR], 6.8; 95% CI, 3.9-12.0) and BSI due to Staphylococcus aureus (HR, 7.2; 95% CI, 3.3-15.7) and lowest among patients with BSI caused by gram-positive bacteria other than S. aureus (HR, 2.2; 95% CI, 1.1-4.6). The risk of death was highest among patients who developed BSI but had the lowest likelihood of infection (HR, 10.0; 95% CI, 3.5-28.8) and was lowest among patients who developed BSI but had the highest likelihood of infection (HR, 2.3; 95% CI, 1.2-4.6). CONCLUSIONS: BSIs due to gram-negative bacteria and BSIs due to S. aureus contributed significantly to mortality. Mortality attributable to BSI was highest among patients predicted to be least likely to develop infection and was lowest among severely ill patients who were most likely to develop infection. BSI appears to be an important contributor to death after coronary artery bypass surgery, particularly among the healthiest patients.

Epidemiology and risk factors for gram-positive coccal infections in neutropenia: toward a more targeted antibiotic strategy.

The objective of this study was to evaluate the risk of acquiring gram-positive coccal infections in febrile neutropenic patients and to develop risk indexes for gram-positive and streptococcal infections. This prospective, multicenter study included 513 patients. The prevalence of gram-positive coccal infections was 21% (14% were staphylococcal infections and 7.8% were streptococcal infections). The mortality rate during the month after study enrollment was 5%. On multivariate analysis, the occurrence of gram-positive coccal infections was significantly associated with receipt of high-dose cytarabine therapy, proton pump inhibitors, and gut decontamination with colimycin without glycopeptides and presence of chills. Staphylococcal infection was significantly associated with use of nonabsorbable colimycin, and streptococcal infection was associated with diarrhea, use of nonabsorbable antifungals, receipt of high-dose cytarabine, and gut decontamination with colimycin. The relative risks for streptococcal infection were 2.9, 13.2, and 20.7 in the presence of 1, 2, and > or =3 parameters, respectively. Risk factors for staphylococcal and streptococcal infections differ among neutropenic patients. A simple scoring system for predicting streptococcal infection is proposed.

Health and economic outcomes of vancomycin-resistant enterococci.

BACKGROUND: The health and economic impact of vancomycin-resistant enterococci has not been quantified. METHODS: A retrospective matched cohort study was conducted comparing the outcomes of patients with vancomycin-resistant enterococci (cases) with those of control subjects matched for length of hospital stay until inclusion in the cohort, hospital location, and calendar date. The propensity to be a vancomycin-resistant enterococci case was modeled based on patient characteristics, and included in multivariable models to adjust for confounding. Analyses included the following: (1) conditional logistic regression for mortality, surgery, intensive care unit admission, and discharge to long-term care; (2) linear regression for the logarithm of cost; and (3) accelerated failure time model for length of stay. RESULTS: A total of 233 cases were compared with 647 controls. Groups were similar in age (mean, 62 years), sex (female, 47%), and length of stay before inclusion in the cohort (mean, 8.1 days), but differed in primary diagnosis and comorbidities, past infection or colonization with methicillin sodium-resistant Staphylococcus aureus or Clostridium difficile, and treatment with cephalosporins or metronidazole. These variables were included in the propensity score, which had good to excellent prediction. Outcomes for cases vs controls and adjusted risks (relative risks [RRs]) were as follows: (1) case fatality rate, 17% vs 6% (RR, 2.13; P =.04); (2) length of stay after inclusion in the cohort, 15.1 vs 8.5 days (RR, 1.73; P<.001); (3) hospital costs, $52 449 vs $31 915 (RR, 1.40; P<.001); (4) surgery after inclusion in the cohort, 18% vs 10% (RR, 2.74; P =.001); (5) intensive care unit admission after inclusion in the cohort, 25% vs 14% (RR, 3.47; P<.001); and (6) transfer to an institution, 51% vs 35% (RR, 2.01; P =.001). CONCLUSION: Compared with a matched hospital population, a population with vancomycin-resistant enterococci was associated with severe adverse outcomes: increased mortality, morbidity, and costs.

Clinical experience of quinupristin-dalfopristin for the treatment of antimicrobial-resistant gram-positive infections.

Data regarding clinical administration, outcomes, and costs of quinupristin-dalfopristin treatment in 48 patients with serious gram-positive infections in a large teaching hospital were analyzed retrospectively. Thirty-six patients had vancomycin-resistant Enterococcus faecium (VREF) infections, 10 had methicillin-resistant Staphylococcus aureus (MRSA) or Staphylococcus epidermidis (MRSE) infections, and 2 were treated empirically Overall, 67% of the patients were clinically cured, and 56% had bacteriologic eradication; overall response rate was 48%. Patients with VREF bacteremia had the highest clinical cure (82%) and bacteriologic eradication (73%) rates. Mortality rate was 31%, but 6 of 15 patients who died were treated successfully with quinupristin-dalfopristin. Length of hospital stay was significantly shorter among patients who lived versus those who died (p<0.05). Similarly, the mean hospital cost/patient was significantly lower in patients who lived than in those who died ($35,244 vs $122,922). Quinupristin-dalfopristin is effective in the treatment of both VREF and MRSA or MRSE infections in patients who fail to respond to, or are intolerant of, vancomycin.

Cost of hospitalization for and risk factors associated with vancomycin-resistant Enterococcus faecium infection and colonization.

The increase in costs of hospitalization for patients with drug-resistant infection may be associated with drug resistance itself or with the severity of the underlying illness that predisposes patients to acquire the drug-resistant infection. To address this issue, risk factors and cost of hospitalization were compared for patients infected or colonized with vancomycin-susceptible Enterococcus faecium (VSEF) or vancomycin-resistant E. faecium (VREF) in a large tertiary-care hospital in New York City. From January 1995 through December 1996, 157 patients with VSEF and 262 patients with VREF were identified. CMI (case-mix index) was assigned to each patient as a measure of severity of illness, with a CMI of 1 considered to represent illness of average severity. For all patients who were assigned a CMI of <3, the cost per day of hospitalization for patients with VREF was significantly greater than that for patients with VSEF. However, for patients with a CMI of >3, there was no difference between cost of hospitalization for patients with VREF and that for patients with VSEF. These observations indicate that, although vancomycin resistance is associated with an increased cost of hospitalization for less severely ill patients with VREF, patients with severe underlying illness, regardless of vancomycin resistance, incur similar hospitalization costs.